The neuropeptide FLFQPQRF-NH2 (F-8-F-NH2) was initially isolated from the bovine brain and found to have morphine modulating activity. F-8-F-NH2 immunoreactive terminals and F-8-F-NH2 receptors were found to be highly localized in the superficial laminae of rat dorsal spinal cords. These observations strongly suggest a role for F-8-F-NH2 in the spinal cord function. In order to explore the functional role of F-8-F-NH2, in this study effects of various transmitters on the secretion of F-8-F-NH2 and the possible interactions between F-8-F-NH2 and opiate mediated responses were investigated in rat spinal cord. Substance P induced the secretion of F-8- F-NH2 from the spinal cord while substance K, norepinephrine and serotonin failed to show such an effect. To explore the possible interaction between F-8-F-NH2 and opiate mediated responses, the secretions of dynorphin and F- 8-F-NH2 from rat spinal cords were studied. The 56 mM KCl evoked secretion of dynorphin was significantly inhibited by the addition of F-8-F-NH2 into the perfusion medium. The 56 mM KCl induced secretion of F-8-F-NH2 was significantly reduced by the addition of naloxone and morphine together into the perfusion medium potentiated the 56 mM KCl evoked F-8-F-NH2 secretion while morphine or naloxone alone showed little effect on the F-8- F-NH2 secretion. The results of this study suggest that F-8-F-NH2 may have a role in the nociceptive transmission and, furthermore, there may be a modulatory role for F-8-F-NH2 in opiate mediated responses.